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Background: European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. Objective: We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. Methods: From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4+CD25+ forkhead box protein 3 (FOXP3)+ (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. Results: Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4+CD25+, FOXP3+ T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. Conclusions: Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases.

Titel:	Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood
Autor/in / Beteiligte Person:	LLUIS, Anna ; DEPNER, Martin ; PFEFFERLE, Petra ; ROPONEN, Marjut ; WEBER, Juliane ; BRAUN-FAHRLÄNDER, Charlotte ; RIEDLER, Josef ; LAUENER, Roger ; VUITTON, Dominique Angèle ; DALPHIN, Jean-Charles ; PEKKANEN, Juha ; VON MUTIUS, Erika ; GAUGLER, Beatrice ; SCHAUB, Bianca ; SAAS, Philippe ; CASACA, Vera Isabel ; RAEDLER, Diana ; MICHEL, Sven ; TOST, Jorg ; JING, LIU ; GENUNEIT, Jon ; Protection Against Allergy: Study in Rural Environments Study Group
Link:	View record from PASCAL Archive
Zeitschrift:	Journal of allergy and clinical immunology, Jg. 133 (2014), Heft 2, S. 551-559
Veröffentlichung:	New York, NY: Elsevier, 2014
Medientyp:	academicJournal
Umfang:	print, 36 ref
ISSN:	0091-6749 (print)
Schlagwort:	Dermatology Dermatologie Immunology, immunopathology, allergology Immunologie, immunopathologie, allergologie Pneumology Pneumologie Sciences biologiques et medicales Biological and medical sciences Sciences biologiques fondamentales et appliquees. Psychologie Fundamental and applied biological sciences. Psychology Immunologie fondamentale Fundamental immunology Sciences medicales Medical sciences Immunopathologie Immunopathology Sarcoidoses. Granulomatoses d'etiologie indeterminee. Maladies du tissu conjonctif. Maladies du tissu elastique. Vascularites Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis Bronchopneumopathie obstructive chronique, asthme Chronic obstructive pulmonary disease, asthma Allergie Allergy Alergia Bronchopneumopathie obstructive Obstructive pulmonary disease Enfermedad pulmonar obstructiva Homme Human Hombre Pathologie de l'appareil respiratoire Respiratory disease Aparato respiratorio patología Pathologie des bronches Bronchus disease Bronquio patología Pathologie des poumons Lung disease Pulmón patología Association Asociación Asthme Asthma Asma Atopie Atopy Atopía Cellule sanguine Blood cell Célula sanguínea Déméthylation Demethylation Desmetilación Enfant Child Niño Exploitation agricole Farming Explotación agrícola Exposition Exposure Exposición Immunologie Immunology Inmunología Inmunopatología Lait Milk Leche Lymphocyte T T-Lymphocyte Linfocito T Mononucléaire Mononuclear cell Mononuclear Sensibilisation Sensitization Sensibilización Cellule régulatrice Regulatory cell Enfance Facteur de transcription FOXP3 Transcription factor FOXP3 FOXP3 demethylation atopic sensitization farming innate milk peripheral blood mononuclear cells regulatory T cells
Sonstiges:	Nachgewiesen in: PASCAL Archive Sprachen: English Original Material: INIST-CNRS Document Type: Article File Description: text Language: English Author Affiliations: LMU Munich, University Children's Hospital, Munich, Germany ; Department of Clinical Chemistry and Molecular Diagnostics, Philipps University of Marburg, South Africa ; Department of Environmental Science. University of Eastern Finland, Kuopio, Finland ; University of Basel, Switzerland ; Swiss Tropical and Public Health Institute, Basel, Switzerland ; Children's Hospital Schwarzach, Schwarzach, Germany ; Christine Kühne-Center for Allergy Research and Education, Hochgebirgklinik Davos, Davos-Wolfgang, Switzerland ; University Hospital of Besançon, Research Unit Health and Rural Environment, University of Franche-Comté, Besançon, France ; Department of Environmental Health, National Institute for Health and Welfare, Kuopio, Finland ; Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland ; University Hospital of Besançon and Plateforme de Biomonitoring, CIC-BT506, EFS Bourgogne Franche-Comté, INSERM UMR1098. University of Franche-Comté, Besançon, France ; University Children's Hospital Eastern Bavaria (KUNO), Department of Pediatric Pneumology and Allergy, University of Regensburg, Germany ; Laboratory for Epigenetics and Environment (LEE), Centre National de Genotypage, CEA-Institut de Genomique, Evry, France ; Second Hospital of JI LIN University, Department of Respiratory Medicine, Chang Chun, China ; Institute of Epidemiology and Medical Biometry, Ulm University, Germany Rights: Copyright 2015 INIST-CNRS ; CC BY 4.0 ; Sauf mention contraire ci-dessus, le contenu de cette notice bibliographique peut être utilisé dans le cadre d’une licence CC BY 4.0 Inist-CNRS / Unless otherwise stated above, the content of this bibliographic record may be used under a CC BY 4.0 licence by Inist-CNRS / A menos que se haya señalado antes, el contenido de este registro bibliográfico puede ser utilizado al amparo de una licencia CC BY 4.0 Inist-CNRS Notes: Fundamental immunology ; Immunopathology ; Pulmonology ; Sarcoidosis. Granulomatosis of undetermined origin. Connective tissue diseases. Vasculitides

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Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood